Barrachina Laura, Remacha Ana Rosa, Romero Antonio, Zaragoza Pilar, Vázquez Francisco José, Rodellar Clementina
Laboratorio de Genética Bioquímica LAGENBIO (Universidad de Zaragoza), Instituto Agroalimentario de Aragón- IA2, (Universidad de Zaragoza-CITA), Instituto de Investigación Sanitaria de Aragón (IIS), C/Miguel Servet, 177, 50013 Zaragoza, Spain; Servicio de Cirugía y Medicina Equina, Hospital Veterinario, Universidad de Zaragoza, C/Miguel Servet, 177. 50013 Zaragoza, Spain.
Laboratorio de Genética Bioquímica LAGENBIO (Universidad de Zaragoza), Instituto Agroalimentario de Aragón- IA2, (Universidad de Zaragoza-CITA), Instituto de Investigación Sanitaria de Aragón (IIS), C/Miguel Servet, 177, 50013 Zaragoza, Spain.
Vet Immunol Immunopathol. 2018 Jun;200:1-6. doi: 10.1016/j.vetimm.2018.04.004. Epub 2018 Apr 14.
Mesenchymal stem cells (MSCs) are a promising treatment for equine musculoskeletal injuries because of their ability to regulate the inflammation and to differentiate into other cell types. Since interest in allogeneic therapy is rising, concerns about MSC immunogenicity need to be addressed. Differentiated MSCs from several species increase their expression of immunogenic molecules and induce alloresponses, but equine MSC immunogenic profile after differentiation has not been reported. Therefore, the aim of this study was to assess the gene expression of immunogenic markers in tri-lineage differentiated equine bone marrow derived MSCs (eBM-MSCs). For this purpose, eBM-MSCs (n = 4) were differentiated into osteoblasts, adipocytes and chondrocytes. Differentiation was confirmed by specific staining and gene expression of lineage-related markers. Subsequently, gene expression of MHC-I, MHC-II, CD40 and CD80 was analyzed in undifferentiated (control) and tri-lineage differentiated eBM-MSCs. Osteogenesis and adipogenesis, but not chondrogenesis, significantly upregulated MHC-I; MHC-II expression significantly increased in the three lineages, while CD40 and CD80 expression did not change. Despite this, MHC-I and MHC-II upregulation after differentiation might lead to increased immunogenicity and risk of allorecognition, either eBM-MSCs differentiate in vivo after administration or they are differentiated prior to administration, with potential negative consequences for effectiveness and safety of allogeneic therapy.
间充质干细胞（MSCs）因其调节炎症和分化为其他细胞类型的能力，有望用于治疗马的肌肉骨骼损伤。由于对同种异体疗法的兴趣日益增加，因此需要解决对MSCs免疫原性的担忧。来自多个物种的分化MSCs会增加其免疫原性分子的表达并诱导同种异体反应，但马MSCs分化后的免疫原性特征尚未见报道。因此，本研究的目的是评估三系分化的马骨髓来源的间充质干细胞（eBM-MSCs）中免疫原性标志物的基因表达。为此，将eBM-MSCs（n = 4）分化为成骨细胞、脂肪细胞和软骨细胞。通过特异性染色和谱系相关标志物的基因表达来确认分化。随后，分析未分化（对照）和三系分化的eBM-MSCs中MHC-I、MHC-II、CD40和CD80的基因表达。成骨和脂肪生成而非软骨生成显著上调了MHC-I；MHC-II表达在三个谱系中均显著增加，而CD40和CD80表达未发生变化。尽管如此，分化后MHC-I和MHC-II的上调可能导致免疫原性增加和同种异体识别风险，无论eBM-MSCs在给药后在体内分化还是在给药前已分化，这都可能对同种异体疗法的有效性和安全性产生潜在的负面影响。
